Apparatus and methods for low-volume medicament delivery

ABSTRACT

Apparatus and methods for delivering medicament. The apparatus may include a fitting for a fluid dispenser. The fitting may include a detent that is configured to limit insertion of the dispenser into the fitting by contacting a terminal surface of the dispenser; and a seal for sealing against the surface. The apparatus may include an insert for the fitting. The insert may include a gasket to seal against the terminal surface of the dispenser; a proximal rim to engage a lateral wall of the dispenser; and a connector fixed to the gasket and the rim. The apparatus may include a coupler to engage a pre-filled dispenser; and a body defining a passageway that is configured to be placed in fluid communication with the dispenser. The apparatus may include a dispenser that includes a detent and a seal. The detent may limit insertion of the dispenser into a fitting.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/912,628, filed on Dec. 6, 2013, which is hereby incorporated byreference herein in its entirety.

BACKGROUND OF THE INVENTION

A medicament in liquid form is commonly delivered into a patient througha needle. A dispenser such as a syringe may be used to deliver themedicament through the needle. The syringe is often connected to theneedle by a connector. The syringe, connector and needle form a pathwayfor delivery of the medicament. Some of the medicament may leave thepathway and enter into void space in the connector and thus not bedelivered to the patient. Often, the void space is small relative to thevolume of medicament that is to be delivered. In such cases, thetherapeutic and economic consequences of losing medicament from thepathway may be acceptable. Sometimes, however, the loss is notacceptable. For example, the void space may be large relative to thevolume of medicament that is to be delivered, the medicament may beexpensive, the loss may make dosing unpredictable because the loss mayvary in volume from one connector to another, among other reasons.

It would be desirable, therefore, to provide apparatus and methods forreducing the loss of medicament from the delivery pathway.

Dispensers such as syringes are often prefilled with a desiredmedicament volume. A practitioner then fully depresses a plunger in thesyringe to deliver the medicament into the patient. Prefilling thesyringe reduces the likelihood of overfilling or underfilling by apractitioner. Fully depressing the plunger of the syringe reduces thelikelihood of underdosing the patient, assuming that the prefilledvolume is correct.

Volumetric precision of prefilling a large volume may be greater thanthe volumetric precision of prefilling a small volume. When it isdesirable to prefill the dispenser for the delivery of a small volume,the lack of volumetric precision may be unacceptable. It would bedesirable, therefore, to provide apparatus and methods for using adispenser to deliver a small volume of the medicament to the patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of apparatus in accordance with theprinciples of the invention;

FIG. 2 is an exploded perspective view of the apparatus shown in FIG. 1,including a partial cross-sectional view of internal features of theapparatus;

FIG. 3 is a partial cross-sectional view of the apparatus shown in FIG.1, the view taken along lines 3-3 (shown in FIG. 1);

FIG. 4 is a partial cross-sectional view of the apparatus shown in FIG.1, the view taken along lines 4-4 (shown in FIG. 1);

FIG. 5 is a partial cross-sectional view of the apparatus shown in FIG.1, the view taken along lines 5-5 (shown in FIG. 1);

FIG. 6 is a cross-sectional view (similar to that of FIG. 3) of theapparatus shown in FIG. 1, along with other apparatus;

FIG. 7 is a cross-sectional view of apparatus in accordance with theprinciples of the invention, along with other apparatus;

FIG. 8 is a cross-sectional view (similar to that of FIG. 4) of theapparatus shown in FIG. 1, along with other apparatus;

FIG. 9 is a cross-sectional view of the apparatus, along with otherapparatus, shown in FIG. 6, the view taken along lines 9-9 (shown inFIG. 6);

FIG. 10 is a cross-sectional view (similar to that of FIG. 9) ofapparatus in accordance with the principles of the invention, along withother apparatus;

FIG. 11 is a partial cross-sectional view of apparatus in accordancewith the principles of the invention;

FIG. 12 is a perspective view of the apparatus shown in FIG. 1, alongwith other apparatus, including a partial cross-sectional view of theother apparatus;

FIG. 13 is an exploded perspective view of apparatus in accordance withthe principles of the invention including partial cross-sectional viewsof the apparatus;

FIG. 14 is a cross-sectional view of the apparatus shown in FIG. 13;

FIG. 15 is a cross-sectional view (similar to that of FIG. 14) ofapparatus in accordance with the principles of the invention;

FIG. 16 is a cross-sectional view of apparatus in accordance with theprinciples of the invention;

FIG. 17 is another cross-sectional view of the apparatus shown in FIG.16;

FIG. 18 is another cross-sectional view of the apparatus shown in FIG.17; and

FIG. 19 shows an illustrative process in accordance with the principlesof the invention.

DETAILED DESCRIPTION OF THE DISCLOSURE

Apparatus and methods for using a dispenser to deliver a small volume ofa medicament to a patient are provided. The apparatus may be used toperform one or more steps of the methods.

The dispenser may be a pre-filled syringe. The apparatus may include afitting to provide fluid communication along a fluid pathway between themedicament dispenser and a needle. The apparatus may include a seal toreduce loss of fluid from the fluid pathway. The seal may be part of thefitting. The seal may be part of the dispenser. The seal may be part ofan insert for the fitting. The apparatus may include a reservoir alongthe fluid pathway. The reservoir may be part of the fitting. Thereservoir may be part of the dispenser. The reservoir may retain fluidto accommodate use of the dispenser when the dispenser has excessmedicament.

The medicament may include a formulation of one or more compounds. Thecompounds may include naturally occurring substances. The compounds mayinclude substances derived from naturally occurring substances. Thecompounds may include synthetically produced substances. The compoundsmay include chimeric substances. The compounds may include engineeredsubstances. The compounds may include humanized substances. Thecompounds may include substances produced by recombinant techniques. Thecompounds may include substances modified by recombinant techniques.

The compounds may include a drug accepted for therapeutic treatment of apatient. The compounds may include a substance used in a therapeuticprotocol. The compounds may include a substance used in a diagnosticprotocol. The compounds may include a substance used in an experimentalprotocol. The compounds may include a substance compatible for use withapparatus and methods of the invention.

Illustrative medicaments that may be used with the apparatus may includeany of those listed herein, either alone or in combination with eachother or with other, non-listed, medicaments. The medicaments mayinclude anti-glaucoma medications, other ocular agents, neuroprotectiveagents, antimicrobial agents, anti-inflammatory agents (includingsteroids and non-steroidal compounds), and biological agents includinghormones, enzymes or enzyme-related components, antibodies orantibody-related components, oligonucleotides (including DNA, RNA,short-interfering RNA, and other suitable oligonucleotides, such asantisense oligonucleotides), DNA/RNA vectors, viruses or viral vectors,peptides, and proteins. The medicaments may include anti-angiogenesisagents, including angiostatin, anecortave acetate, thrombospondin,vascular endothelial growth factor (VEGF) receptor tyrosine kinaseinhibitors, and anti-VEGF drugs, such as ranibizumab (LUCENTIS®),bevacizumab (AVASTIN®), pegaptanib (MACUGEN®), sunitinib, and sorafenib,and any of a variety of known small-molecule and transcriptioninhibitors having an anti-angiogenesis effect; ophthalmic drugs,including glaucoma agents, such as adrenergic antagonists, includingbeta-blocker agents such as atenolol, propranolol, metipranolol,betaxolol, carteolol, levobetaxolol, levobunolol and timolol. Themedicaments may include anti-inflammatory agents includingglucocorticoids and corticosteroids, such as betamethasone, cortisone,dexamethasone, dexamethasone 21-phosphate, methylprednisolone,prednisolone 21-phosphate, prednisolone acetate, prednisolone,loteprednol, medrysone, fluocinolone acetonide, triamcinolone acetonide,triamcinolone, beclomethasone, budesonide, flunisolide, fluorometholone,fluticasone, hydrocortisone, hydrocortisone acetate and rimexolone; andnon-steroidal anti-inflammatory agents including diclofenac,flurbiprofen, ibuprofen, bromfenac, nepafenac, ketorolac, salicylate,indomethacin, naxopren, naproxen, piroxicam and nabumetone. Themedicaments may include anti-complement agents, including thosetargeting complement factor D (such as an anti-complement factor Dantibody or an antigen-binding fragment thereof) and those targetingcomplement factor H (such as an anti-complement factor H antibody or anantigen-binding fragment thereof).

In descriptions herein of apparatus and methods of the invention, theterm “seal” and the term “gasket” may be used interchangeably. Indescriptions herein of apparatus and methods of the invention, functionsof the reservoir may be performed by a void or passageway in fluidcommunication with the fitting.

Fitting

The fitting may receive the end of the dispenser to place the dispenserin fluid communication with the needle. The fitting may have alongitudinal axis. The fitting may include a detent. The detent may beconfigured to limit longitudinal insertion of the dispenser into thefitting. The limitation may be effected by application, by the detent,of a longitudinal contact force against a terminal surface of thedispenser.

Prior to the fitting receiving the end of the dispenser, the seal may bein a relaxed state. The seal may be configured to be deformed by theinserted terminal surface of the dispenser. The seal may be configuredto be deformed into sealing contact against the terminal surface. Theseal may be deformed into sealing contact against the terminal surfacewhen the terminal surface abuts, or lodges against, the detent. Wereapplication of the longitudinal contact force to cease, the seal may beconfigured to return substantially to its relaxed state.

The seal may include a first seal material. The first seal material mayinclude rubber. The first seal material may include silicone. The firstseal material may include a thermoplastic elastomer (TPE). The firstseal material may include a polymeric substance. The first seal materialmay include a material with a hardness less than about 200 Shore Adurometer (ASTM D2240 type A hardness scale).

The seal may include a second seal material. The second seal materialmay include polytetrafluoroethylene (PTFE). The second seal material mayinclude ethylene tetrafluoroethylene (ELTFE). The second seal materialmay coat the first seal material. The second seal material may include amaterial selected to reduce interaction of the seal with a medicament.

The seal may be configured such that the seal would not returnsubstantially to its relaxed state upon cessation of application of thelongitudinal contact force. The seal may be configured to remainsubstantially deformed. The seal may be configured for one-time use.

The seal may be configured to be crushed to provide sealing contactbetween the fitting and the dispenser. The seal may be configured as acrushable bib between the fitting and the dispenser. Prior to thefitting receiving the end of the dispenser, the crushable bib may beassociated with the dispenser. Prior to the fitting receiving the end ofthe dispenser, the crushable bib may be associated with the fitting.

The fitting may include a body. The body may be configured to receivethe terminal surface of the dispenser. The body may be configured tosupport the detent. The detent may lie within a plane disposed on aportion of the body. The detent may overlie a portion of the body. Thedetent may be a portion of the body. The detent may be within the body.

The body may include a body material. The body material may includepolypropylene (hereinafter, “PP”). The body material may includepolyethylene (hereinafter, “PE”). The body material may includepolycarbonate (hereinafter, “PC”). The body material may include a rigidmaterial. The body material may include a semi-rigid material. The bodymaterial may include a transparent material. The body material mayinclude a translucent material. The body material may include an opaquematerial. The body material may include a material that is chemicallyinert. The body material may include a material that is chemicallystable. The body material may include a material selected for havingminimum interaction with a medicament.

The body may be configured to support the seal. The seal may be aportion of the body. The seal may be installed in the body. The seal maybe within the body.

The seal may circumscribe the detent. The detent may circumscribe theseal.

The fitting may define an opening. The opening may be configured to beplaced in fluid communication with the dispenser. The opening may betransverse to the longitudinal axis. The longitudinal axis may runthrough the opening. The longitudinal axis may run through the center ofthe opening. The detent may define the opening. The seal may define theopening.

The fitting may include an interior wall. The interior wall may be aninterior circumferential wall of the body. The interior circumferentialwall may have a cylindrical axis. When the dispenser is coupled to thefitting, the cylindrical axis may be collinear with the longitudinalaxis of the fitting.

The dispenser may include a lateral wall. The lateral wall may be anexterior circumferential wall of the dispenser. When the dispenser is asyringe, the lateral wall may be an exterior circumferential wall of asyringe barrel. A portion of the wall of the barrel may be complementaryto the interior circumferential wall of the body. The portion may bereceived within the interior circumferential wall of the body. Theportion may be received within the interior circumferential wall of thebody through longitudinal insertion of the dispenser into the fitting.

The dispenser may have a distal end. The distal end may have a distaltip. The lateral wall may be an exterior circumferential wall of thedistal tip. A portion of the exterior circumferential wall of the distaltip may be complementary to the interior circumferential wall of thebody. A portion of the exterior circumferential wall of the distal tipmay be received within the interior circumferential wall of the body.The portion of the exterior circumferential wall of the distal tip maybe received within the interior circumferential wall of the body throughlongitudinal insertion of the dispenser into the fitting.

The distal end of the dispenser may have a distal-most face. Theterminal surface of the dispenser may coincide with the distal-most faceof the dispenser.

The dispenser may include a dispenser material. The dispenser materialmay include glass. The dispenser material may include a polymericsubstance. The dispenser material may include a crystalline polymer. Thedispenser material may include an amorphous polymer. The dispensermaterial may include a cyclic olefin polymer (COP). The dispensermaterial may include a cyclic olefin copolymer (COC). The dispensermaterial may include PP. The dispenser material may include PE. Thedispenser material may include PC. The dispenser material may include atransparent material. The dispenser material may include a translucentmaterial. The dispenser material may include an opaque material. Thedispenser material may include a material that is chemically inert. Thedispenser material may include a material that is chemically stable. Thedispenser material may include a material selected for having minimuminteraction with a medicament.

The distal-most face of the dispenser may define an aperture in fluidcommunication with an interior volume of the dispenser. The aperture maybe in fluid communication with a bore of the syringe. The distal end ofthe dispenser may be received by the fitting through longitudinalinsertion, distal-end first, of the dispenser into the fitting.Insertion of the distal end of the dispenser into the fitting may belimited by the distal-most face coming into contact with the detentsupported by the body. The dispenser may be selected, or may bemodified, so that the distal-most face of its distal end may come intocontact with the detent upon longitudinal insertion into the fitting.

When the terminal surface of the dispenser is in sealing contact againstthe seal, a volumetric region may be defined by the interior wall of thefitting, the lateral wall of the dispenser and the seal. When theterminal surface of the dispenser abuts the detent, the interior wall,the lateral wall and the seal may define the region. When the terminalsurface of the dispenser is in sealing contact against the seal andabuts the detent, the interior wall, the lateral wall and the seal maydefine the region.

The region may be isolated from fluid communication with the dispenser.The sealing contact may be sufficient to prevent leakage of fluid fromthe dispenser to the region when the dispenser is actuated to dispensethe fluid. The region may be isolated from fluid communication with theopening. The sealing contact may be sufficient to prevent leakage offluid from the opening to the region when the dispenser is actuated todispense the fluid.

The region may be a first dead space. The first dead space may have afirst volume.

When the detent is in contact with the terminal surface of thedispenser, the detent may define a second dead space. The second deadspace may include one or more volumes in a region that is transverselycoextensive with contact of the detent and the surface and thatlongitudinally extends between the detent and the surface. The seconddead space may be bordered by an inner annular boundary of the seal.

The second dead space may have a second volume. The second volume may beno more than 1% the first volume. The second volume may be no more than0.1% the first volume.

The body of the fitting may define a void. The void may be a reservoir.The void may be a passageway. The void may be in fluid communicationwith the opening. The void may have a void volume.

The dispenser may be pre-filled with an initial volume of the fluid. Thevoid volume may be not less than 10% the initial volume of fluid in thedispenser. The void volume may be not less than 25% the initial volume.The void volume may be not less than 50% the initial volume. The voidvolume may be not less than 75% the initial volume. The void volume maybe not less than 90% the initial volume.

The fitting may support the needle. The needle may be in fluidcommunication with the void. Fluid may be dispensed through an orificeof the needle. The orifice may be a delivery orifice of the needle. Avolume of fluid dispensed through the orifice may be the initial volumereduced by an amount. The amount may be not less than the void volume.The amount may include a volume remaining in the dispenser after thefluid is dispensed. The amount may include a volume of a bore of theneedle.

The seal may be annular. The seal may be rectilinear. The seal may beany shape that provides effective sealing.

The seal may include a proximal face. The seal may include a distalface. The distal face may be spaced apart from the proximal face. Theproximal face and the distal face may be substantially parallel.

The seal may include an outer surface. The outer surface may extend inthe longitudinal direction. The seal may include an inner surface. Theinner surface may extend in the longitudinal direction.

The distal face and the inner surface may intersect at an angle of about90°. The distal face and the inner surface may intersect at an anglethat may range from about 80° to about 89°. The distal face and theinner surface may intersect at an angle that may range from about 70° toabout 79°. The distal face and the inner surface may intersect at anangle that may range from about 60° to about 69°. The distal face andthe inner surface may intersect at an angle that may range from about50° to about 59°. The distal face and the inner surface may intersect atan angle that may range from about 40° to about 49°. The distal face andthe inner surface may intersect at an angle that may range from about91° to about 100°. The distal face and the inner surface may intersectat an angle that may range from about 101° to about 110°. The distalface and the inner surface may intersect at an angle that may range fromabout 111° to about 120°. The distal face and the inner surface mayintersect at an angle that may range from about 121° to about 130°. Thedistal face and the inner surface may intersect at an angle that mayrange from about 131° to about 140°.

The distal face and the inner surface may be configured such that theydo not intersect. One or more other seal surfaces may lie between thedistal face and the inner surface. The other seal surfaces may connectthe distal face and the inner surface. The other seal surfaces may formone or more corners between the distal face and the inner surface.

The distal face and the outer surface may intersect at an angle of about90°. The distal face and the outer surface may intersect at an anglethat may range from about 80° to about 89°. The distal face and theouter surface may intersect at an angle that may range from about 70° toabout 79°. The distal face and the outer surface may intersect at anangle that may range from about 60° to about 69°. The distal face andthe outer surface may intersect at an angle that may range from about50° to about 59°. The distal face and the outer surface may intersect atan angle that may range from about 40° to about 49°. The distal face andthe outer surface may intersect at an angle that may range from about91° to about 100°. The distal face and the outer surface may intersectat an angle that may range from about 101° to about 110°. The distalface and the outer surface may intersect at an angle that may range fromabout 111° to about 120°. The distal face and the outer surface mayintersect at an angle that may range from about 121° to about 130°. Thedistal face and the outer surface may intersect at an angle that mayrange from about 131° to about 140°.

The distal face and the outer surface may be configured such that theydo not intersect. One or more other seal surfaces may lie between thedistal face and the outer surface. The other seal surfaces may connectthe distal face and the outer surface. The other seal surfaces may formone or more corners between the distal face and the outer surface.

The proximal face and the inner surface may intersect at an angle ofabout 90°. The proximal face and the inner surface may intersect at anangle that may range from about 80° to about 89°. The proximal face andthe inner surface may intersect at an angle that may range from about70° to about 79°. The proximal face and the inner surface may intersectat an angle that may range from about 60° to about 69°. The proximalface and the inner surface may intersect at an angle that may range fromabout 50° to about 59°. The proximal face and the inner surface mayintersect at an angle that may range from about 40° to about 49°. Theproximal face and the inner surface may intersect at an angle that mayrange from about 91° to about 100°. The proximal face and the innersurface may intersect at an angle that may range from about 101° toabout 110°. The proximal face and the inner surface may intersect at anangle that may range from about 111° to about 120°. The proximal faceand the inner surface may intersect at an angle that may range fromabout 121° to about 130°. The proximal face and the inner surface mayintersect at an angle that may range from about 131° to about 140°.

The proximal face and the inner surface may be configured such that theydo not intersect. One or more other seal surfaces may lie between theproximal face and the inner surface. The other seal surfaces may connectthe proximal face and the inner surface. The other seal surfaces mayform one or more corners between the proximal face and the innersurface.

The proximal face and the outer surface may intersect at an angle ofabout 90°. The proximal face and the outer surface may intersect at anangle that may range from about 80° to about 89°. The proximal face andthe outer surface may intersect at an angle that may range from about70° to about 79°. The proximal face and the outer surface may intersectat an angle that may range from about 60° to about 69°. The proximalface and the outer surface may intersect at an angle that may range fromabout 50° to about 59°. The proximal face and the outer surface mayintersect at an angle that may range from about 40° to about 49°. Theproximal face and the outer surface may intersect at an angle that mayrange from about 91° to about 100°. The proximal face and the outersurface may intersect at an angle that may range from about 101° toabout 110°. The proximal face and the outer surface may intersect at anangle that may range from about 111° to about 120°. The proximal faceand the outer surface may intersect at an angle that may range fromabout 121° to about 130°. The proximal face and the outer surface mayintersect at an angle that may range from about 131° to about 140°.

The proximal face and the outer surface may be configured such that theydo not intersect. One or more other seal surfaces may lie between theproximal face and the outer surface. The other seal surfaces may connectthe proximal face and the outer surface. The other seal surfaces mayform one or more corners between the proximal face and the outersurface.

The seal may have a cross-section. The cross-section may include asubstantially square profile. The cross-section may include asubstantially rectangular profile. The cross-section may havesubstantially perpendicular corners. The cross-section may besubstantially trapezoidal. The cross-section may have substantiallyrounded corners. The cross-section may be substantially circular. Thecross-section may be substantially ovoid. The cross-section may besubstantially ellipsoid. The cross-section may include any combinationof straight lines and/or curves that provides effective sealing.

The fitting may include a base portion. The detent and the seal mayextend longitudinally from the base portion in a proximal direction. Thedetent may include a top. The seal, in a relaxed state, may extendproximally beyond the top. The seal may not extend transversely over thetop.

The base portion may define a recess. The recess may be configured toreceive the seal. The recess may have a cross-section that iscomplementary to a portion of the cross-section of the seal. The recessmay be configured to secure the seal. The seal may be secured such thata proximal end of the seal does not relax over the top.

When the terminal surface of the dispenser abuts the detent, theterminal surface may be perpendicular to the longitudinal axis of thefitting. When the terminal surface of the dispenser abuts the detent,the terminal surface may be at an orientation other than perpendicularto the longitudinal axis of the fitting.

When the terminal surface of the dispenser abuts the detent, theterminal surface may be oriented to the longitudinal axis at an anglethat may range from about 80° to about 89°. When the terminal surface ofthe dispenser abuts the detent, the terminal surface may be oriented tothe longitudinal axis at an angle that may range from about 70° to about79°. When the terminal surface of the dispenser abuts the detent, theterminal surface may be oriented to the longitudinal axis at an anglethat may range from about 60° to about 69°. When the terminal surface ofthe dispenser abuts the detent, the terminal surface may be oriented tothe longitudinal axis at an angle that may range from about 50° to about59°. When the terminal surface of the dispenser abuts the detent, theterminal surface may be oriented to the longitudinal axis at an anglethat may range from about 40° to about 49°. When the terminal surface ofthe dispenser abuts the detent, the terminal surface may be oriented tothe longitudinal axis at an angle that may range from about 91° to about100°. When the terminal surface of the dispenser abuts the detent, theterminal surface may be oriented to the longitudinal axis at an anglethat may range from about 101° to about 110°. When the terminal surfaceof the dispenser abuts the detent, the terminal surface may be orientedto the longitudinal axis at an angle that may range from about 111° toabout 120°. When the terminal surface of the dispenser abuts the detent,the terminal surface may be oriented to the longitudinal axis at anangle that may range from about 121° to about 130°. When the terminalsurface of the dispenser abuts the detent, the terminal surface may beoriented to the longitudinal axis at an angle that may range from about131° to about 140°.

When the terminal surface of the dispenser abuts the detent, theterminal surface may be at an orientation to the longitudinal axis ofthe fitting at any angle that lodges the terminal surface of thedispenser against the detent. When the terminal surface of the dispenserabuts the detent, the terminal surface may be at an orientation to thelongitudinal axis of the fitting at any angle that provides effectivesealing of the seal against the terminal surface.

The detent may have a first contour. The terminal surface of thedispenser may have a second contour. The first contour and the secondcontour may be complementary. The seal may have a third contour. Thesecond contour and the third contour may be complementary.

The seal may include a first substance. The first substance may includethe first seal material. The first substance may include the second sealmaterial. The first substance may have a first elastic modulus. Thedetent may include a second substance. The second substance may includethe body material. The second substance may have a second elasticmodulus. The second elastic modulus may be greater than the firstelastic modulus.

The terminal surface of the dispenser may be disposed on a portion ofthe dispenser that includes a third substance. The third substance mayinclude the dispenser material. The third substance may have a thirdelastic modulus. The third elastic modulus may be about the same as thesecond elastic modulus.

The fitting may include an engagement member. The engagement member maybe configured to maintain the sealing contact. The engagement member maymaintain the sealing contact by engaging the dispenser. The dispensermay have a complementary engagement surface that the engagement membermay engage. The engagement member may be a Luer-style surface in thefitting. The dispenser may have a complementary engagement surface thatmay engage the Luer-style surface of the fitting. The Luer-style surfaceof the fitting and the complementary surface of the dispenser may be ofa Luer lock variety. The Luer-style surface of the fitting and thecomplementary surface of the dispenser may be of a Luer slip variety.

The fitting may include one or more bosses. The one or more bosses maybe associated with the interior wall of the fitting. Each of the one ormore bosses may be configured to extend radially inward relative to thecylindrical axis from the interior circumferential wall of the fitting.The one or more bosses may be configured to engage the dispenser. Theone or more bosses may be configured to engage the lateral wall of thedispenser.

The fitting may be configured to engage a needle guard. The guard maycover the needle prior to dispensing the fluid. The guard may beconfigured to be disassociated from the fitting prior to dispensing thefluid.

The fitting may be packaged for use by a practitioner with the needleguard engaged with the fitting. The dispenser may be packaged for use bythe practitioner pre-filled with the initial volume of the fluid. Thefitting may be packaged for use together with the pre-filled dispenser.Packaging may maintain sterility of the packaged items.

The pre-filled dispenser may be capped by a cap. The cap may be removedfrom the dispenser prior to the fitting being engaged with thedispenser. The needle guard may be removed from the fitting subsequentto the fitting being engaged with the dispenser.

The seal and the fitting may be a unitary piece. The unitary piece mayinclude a fourth substance. The unitary piece may be semi-rigid. Theseal may be integral to the fitting. The fourth substance may have anelastic modulus less than the second elastic modulus and greater thanthe first elastic modulus.

Insert

The insert may engage the terminal surface of the dispenser. The insertmay engage the lateral wall of the dispenser when the fitting receivesthe dispenser. The insert may be seated in the fitting.

The insert may include a first material. The first material of theinsert may include the first seal material. The first material of theinsert may include the second seal material. The fitting may include asecond material. The second material of the fitting may include the bodymaterial. The first material of the insert may be more compliant thanthe second material of the fitting. The insert may include a distalgasket. The gasket may be configured to seal against a terminal surfaceof a dispenser. The gasket may have one or more features in common withthe seal.

The insert may include a proximal rim. The proximal rim may beconfigured to engage a lateral wall of the dispenser. The proximal rimengaging the lateral wall of the dispenser may supplement otherengagement of the lateral wall. Other engagement of the lateral wall maybe achieved through urging the gasket against the terminal surface. Theproximal rim urging the gasket against the terminal surface maysupplement any urging of the gasket against the terminal surface thatmay be achieved through engagement of the fitting with the dispenser

The insert may include one or more connectors. Each of the one or moreconnectors may be distally fixed to the gasket. Each of the one or moreconnectors may be proximally fixed to the rim. The gasket and the rimmay be substantially parallel. The gasket and the rim may be mutuallyoriented in a non-parallel orientation. The gasket and the rim may bespaced apart, at least in part, by the one or more connectors. Each ofthe one or more connectors may have at least one substantiallylongitudinal member. The at least one longitudinal member may be fixedto the rim. Each of the one or more connectors may have at least onesubstantially transverse member. The at least one transverse member maybe fixed to the gasket.

The gasket may be configured to be seated in a recess in the fitting.Each of the one or more connectors may be configured to be seated in arecess in the fitting.

The rim may be configured to conform to a flange of the fitting. The rimmay be configured to conform to the engagement member. The flange of thefitting may be associated with a proximal edge of a circumferential wallof the fitting. The engagement member may be associated with a proximalend of the fitting. The proximal edge may be associated with theproximal end.

The one or more connectors may be configured to transmit force betweenthe gasket and the rim. The force may urge the gasket against theterminal surface of the dispenser. The connector may urge the gasketagainst the terminal surface by transmitting the force between thegasket and the rim. The force may urge the rim against the lateralsurface of the dispenser. The connector may urge the rim against thelateral surface by transmitting the force between the gasket and therim.

The insert may be molded onto the fitting. The molding may beaccomplished through an overmolding process. The molding may beaccomplished through a coinjection process. The recesses into which theconnectors may be seated may expedite molding of the insert. Therecesses may provide channels for a seal material of the insert,injectable during a molding process, to flow between the proximal end ofthe fitting and the recess into which the gasket may be seated. Theinjectable seal material may form the gasket. The injectable materialmay form the rim. The rim may be a remnant of the molding process of thegasket. The injectable material may form the one or more connectors. Theone or more connectors may be remnants of the molding process of thegasket. The one or more connectors may be configured to not transmit theforce between the gasket and the rim.

Reservoir

The reservoir may retain a volume of fluid when the dispenser isactuated to dispense fluid. The reservoir may include a coupler. Thecoupler may have one or more features in common with the fitting. Thecoupler may have one or more features in common with the seal. Thecoupler may sealingly engage a dispenser. The dispenser may bepre-filled with an initial volume of fluid. The reservoir may beincluded in the fitting. The reservoir may be included in the dispenser.When the reservoir is included in the dispenser, the fitting may beconfigured such that it does not include a reservoir.

The reservoir may include the passageway. The passageway may beconfigured to be placed in fluid communication with the dispenser. Thepassageway may lead to a hypodermic needle. The needle may be in fluidcommunication with the passageway.

The passageway may have a volume. The volume of the passageway may benot less than 10% of the initial volume of fluid in the dispenser. Thevolume of the passageway may be not less than 25% of the initial volume.The volume of the passageway may be not less than 50% of the initialvolume. The volume of the passageway may be not less than 75% of theinitial volume. The volume of the passageway may be not less than 90% ofthe initial volume.

Fluid may be dispensed through a delivery orifice of the hypodermicneedle. The volume of fluid dispensed through the delivery orifice maybe the initial volume reduced by an amount. The amount may be not lessthan the volume of the passageway.

The methods for low volume medicament delivery may involve dispensing adose volume of substance from the dispenser. The dispenser may bepre-filled with an initial volume of the substance. The substance mayinclude the medicament.

The methods may include a multi-stage discharging of liquid from thedispenser. A first stage may include discharging a priming volume fromthe dispenser. The priming volume may be discharged by depressing aplunger of the dispenser to a first mechanically indexed position withinthe bore of the dispenser. The first position may be indexed by a collaron a proximal end of a shaft of the plunger. The collar may beconfigured to allow the plunger to be advanced distally within the boresufficiently, and no more than is required, to drive the priming volumeout of the bore. The collar may be removed from the shaft after thepriming volume is discharged from the bore. At least part of the primingvolume may be driven into the reservoir. At least part of the primingvolume may be driven into the needle.

A second stage may include depressing the plunger to a secondmechanically indexed position within the bore. The second position maybe indexed by the proximal end of the shaft contacting a proximal end ofthe dispenser. The second position may be indexed by the proximal end ofthe shaft contacting a proximal end of the bore. The second position maybe indexed by the proximal end of the shaft contacting stop surfaceexternal to the bore. The second position may be indexed by a distal endof the shaft contacting a stop shoulder internal to the bore. The distalend of the shaft may include a plunger plug. The second position mayaccommodate a maximum stroke of the plunger within the bore.

The volume of fluid discharged from the dispenser in the second stagemay be the dose volume. The dose volume may correspond to the initialprefilled volume minus the priming volume.

The method may include retaining a reservoir volume in the reservoir.The reservoir volume may be part of the priming volume. The reservoirvolume may be not less than 10% of the initial volume of substance withwhich the dispenser may be pre-filled. The reservoir volume may be notless than 25% of the initial volume. The reservoir volume may be notless than 50% of the initial volume. The reservoir volume may be notless than 75% of the initial volume. The reservoir volume may be notless than 90% of the initial volume.

The reservoir may be in fluid communication with the dispenser. Thereservoir may be in fluid communication with a needle. The needle mayinclude a delivery orifice.

The method may include dispensing the dose volume through the deliveryorifice of the needle. The dose volume may be the initial volume reducedby an amount. The amount may be not less than the reservoir volume.

Dispenser

A fluid dispenser may be configured to include a seal for sealinglyengaging a fitting. The fluid dispenser may include the dispensermaterial. The fitting may include the body material. The seal mayinclude the first seal material. The seal may include the second sealmaterial. The fluid dispenser may have a distal end that includes theseal. When the distal end includes the seal, the fitting may beconfigured such that it does not include a seal.

The distal end may include a detent. The detent may be transverse to thelongitudinal axis of the dispenser. The detent may be configured tolimit longitudinal insertion of the dispenser into a fitting.Longitudinal insertion of the dispenser into the fitting may be limitedby the detent applying a longitudinal contact force against a proximalsurface of the fitting.

The seal may be configured to be deformed by the proximal surface of thefitting. The seal may be configured to be deformed into sealing contactagainst the surface. The seal may be deformed into sealing contactagainst the surface when the detent lodges against the surface.

The distal end may include a terminal portion. The terminal portion maybe configured to be received by the fitting. The terminal portion may beconfigured to support the detent. The terminal portion may be configuredto support the seal. The seal may circumscribe the detent. The detentmay circumscribe the seal.

The distal end detent may define an aperture. The detent may define anaperture. The aperture may be in fluid communication with a bore of thedispenser. The fitting may define a passageway configured to be placedin fluid communication with the aperture.

The terminal portion may include an exterior lateral wall. The fittingmay include an interior wall. When the seal may be in sealing contactagainst the proximal surface of the fitting and the detent may abut thesurface, the exterior wall, the interior wall and the seal may define aregion.

The sealing contact may be sufficient to prevent leakage of fluid fromthe dispenser to the region when the dispenser may be actuated todispense the fluid. The region may be isolated from fluid communicationwith the dispenser.

The region may be a first dead space. The first dead space may have afirst volume.

When the detent is in contact with the proximal surface of the fitting,the detent may define a second dead space. The second dead space mayinclude one or more volumes in a region that may be transverselycoextensive with contact between the detent and the surface and may belongitudinally extensive between the detent and the surface. The seconddead space may be within the seal.

The second dead space may have a second volume. The second volume may beno more than 1% the first volume. The second volume may be no more than0.1% the first volume.

The detent and the seal may extend longitudinally from a section of theterminal portion in a distal direction. The detent may include a bottom.The seal, in a relaxed state, may extend distally beyond the bottom. Theseal may not extend transversely under the bottom.

The terminal portion section may define a recess. The recess may beconfigured to secure the seal. The recess may be annular. The seal maybe annular. The seal may be configured to engage the recess. The sealmay circumferentially engage the recess. The seal may adhere to asurface of the recess. The seal may be secured such that a distal end ofthe seal may not be drawn laterally under the bottom.

When the detent lodges against the proximal surface of the fitting, thesurface may be perpendicular to the longitudinal axis of the dispenser.

The detent may have a first contour. The proximal surface of the fittingmay have a second contour. The first contour and the second contour maybe complementary. The seal may have a third contour. The second contourand the third contour may be complementary.

The proximal surface of the fitting may be disposed on a portion of thefitting having a third elastic modulus. The third elastic modulus may beabout the same as the second elastic modulus.

The dispenser may include an engagement member. The engagement membermay be configured to maintain the sealing contact. The engagement membermay maintain the sealing contact by engaging the fitting.

The dispenser may include a glass syringe.

The bore of the dispenser may have a bore diameter. The dispenser mayinclude a plunger. The plunger may have a plunger plug. The plunger plugmay have a diameter about the same as the bore diameter. The plungerplug may be slideably disposed within the bore. The plunger plug may bemoved within the bore longitudinally distally toward the aperture from aproximal position. Longitudinal movement of the plunger plug toward theaperture may drive fluid in the bore toward the aperture.

The bore may include a shoulder jutting radially into the bore. Theshoulder may be annular. The shoulder may have an inner annular diametersmaller than the bore diameter. The shoulder may be located between theplunger plug and the aperture. Movement of the plunger plug within thebore to the aperture may be stopped by the shoulder.

A volume of the bore between the shoulder and the aperture may serve apurpose similar to that of the reservoir, void or passageway describedabove.

The fitting may include a detent, a seal and a reservoir (or void).Alternatively, the dispenser may include the detent, the seal and thereservoir (or void). In other embodiments, only one of the detent, theseal and the reservoir may be in the fitting, with the others being inthe dispenser. In yet other embodiments, two of the detent, the seal andthe reservoir may be in the fitting, with the other being in thedispenser.

Apparatus and methods in accordance with the invention will now bedescribed in connection with the FIGS. The FIGS. show illustrativefeatures of apparatus and methods in accordance with the principles ofthe invention. The features are illustrated in the context of selectedembodiments. It will be understood that features shown in connectionwith one of the embodiments may be practiced in accordance with theprinciples of the invention along with features shown in connection withanother of the embodiments.

Apparatus and methods described herein are illustrative. Apparatus andmethods of the invention may involve some or all of the features of theillustrative apparatus and/or some or all of the steps of theillustrative methods. The steps of the methods may be performed in anorder other than the order shown and described herein. Some embodimentsmay omit steps shown and described in connection with the illustrativemethods. Some embodiments may include steps that are not shown anddescribed in connection with the illustrative methods.

Illustrative embodiments will now be described with reference to theaccompanying drawings, which form a part hereof.

The apparatus and methods of the invention will be described inconnection with embodiments and features of illustrative devices. Thedevices will be described now with reference to the FIGS. It is to beunderstood that other embodiments may be utilized and structural,functional and procedural modifications may be made without departingfrom the scope and spirit of the present invention.

FIG. 1 shows illustrative device 100. Device 100 may define longitudinalaxis L.

Device 100 may include fitting 110. Device 100 may include insert 102.FIG. 1 shows that insert 102 may be seated in fitting 110.

Device 100 may include needle 130. Needle 130 may be supported byfitting 110. Needle 130 may be in fluid communication with fitting 110.Needle 130 may be a hypodermic needle. Needle 130 may be parallel toaxis L.

FIG. 2 shows that insert 102 may include distal gasket 204. Gasket 204may be annular.

Gasket 204 may include proximal face 205. Gasket 204 may include distalface 203. Face 203 and face 205 may be substantially parallel to eachother. Face 203 and face 205 may be spaced apart by thickness t.

Insert 102 may include proximal rim 208. Rim 208 and gasket 204 may besubstantially parallel to each other.

Insert 102 may include one or more connectors between rim 208 and gasket204. For example, insert 102 may include connector 206. Rim 208 andgasket 204 may be spaced apart by connector 206. Connector 206 may beconnected proximally to rim 208. Connector 206 may be connected distallyto gasket 204.

Connector 206 may include transverse member 201. Connector 206 mayinclude longitudinal member 207. Member 201 may be connected to member207. Member 201 and member 207 may be components of a unitary body.Member 201 may be connected to gasket 204. Member 207 may be connectedto rim 208. Rim 208, gasket 204 and connector 206 may be components ofthe unitary body. The unitary body may include insert 102.

Insert 102 may be seated in fitting 110 (as shown in FIG. 1). Rim 208may be separately seated in fitting 110 (not shown). Gasket 204 may beseparately seated in fitting 110 (not shown).

Fitting 110 may include body 211. Body 211 may include flange 216. Rim208 may engage flange 216. Body 211 may include engagement member 219.Rim 208 may engage engagement member 219.

Body 211 may include interior wall 209. Interior wall 209 may includelongitudinal recess 214. Connector 206 may be seated in recess 214.Member 207 may be seated in recess 214.

Body 211 may include recess 212. Recess 212 may be complementary to adistal portion of gasket 204. Recess 212 may be annular. Gasket 204 maybe seated in recess 212. When gasket 204 is seated in recess 212, face203 may contact distal bottom 215 of recess 212.

Body 211 may include facet 210. Body 211 may include base portion 213.Base portion 213 may include recess 212. When gasket 204 is seated inrecess 212, base portion 213 may support gasket 204.

Base portion 213 may support detent 218. Detent 218 may define opening222. Detent 218 may circumscribe opening 222.

Body 211 may include void 220. Opening 222 may be a proximal end of void220. Opening 222 may be in fluid communication with void 220.

Body 211 may include floor 224. Floor 224 may be a distal boundary ofvoid 220. Floor 224 may include needle inlet 234. Needle inlet 234 maybe connected with needle 130.

Needle 130 may include needle bore 236. Bore 236 may be in fluidcommunication with inlet 234. Needle 130 may include delivery orifice232. Orifice 232 may be in fluid communication with bore 236.

FIG. 3 is a cross-sectional view taken along lines 3-3 (shown in FIG.1). FIG. 3 shows that gasket 204 may be seated in recess 212. Gasket 204may circumscribe detent 218. Detent 218 may include detent top 317.Gasket 204 may extend longitudinally from recess 212 in a proximaldirection beyond top 317.

FIG. 4 is a cross-sectional view taken along lines 4-4 (shown in FIG.1). FIG. 4 shows that body 211 may include transverse recess 415. Recess415 may be continuous with recess 212. Recess 415 may be continuous withrecess 214.

FIG. 4 shows that gasket 204 may be seated in recess 212. Gasket 204 maybe connected to member 201. Member 201 may be seated in recess 415.Member 201 may be connected to member 207. Member 207 may be seated inrecess 214. Member 207 may be connected to rim 208.

FIG. 5 is a cross-sectional view taken along lines 5-5 (shown in FIG.1). FIG. 5 shows that gasket 204 may be seated within fitting 110.

Orifice 232 may be distal-most in this view. Orifice 232 may be at adistal end of needle 130. Needle 130 may be in fluid communication withinlet 234. Floor 224 may define inlet 234. Floor 224 may be the distalboundary of void 220. Floor 224 may be distal to opening 222. Void 220may be in fluid communication with opening 222. Detent 218 maycircumscribe opening 222. Gasket 204 may circumscribe detent 218. Gasket204 may connect to member 201. Member 201 may connect to member 207.Member 201 may be distal to member 207. Member 207 may be seated inrecess 214.

In this view, member 201 may be distal to top 317. Top 317 may be distalto face 205.

FIG. 6 shows fitting 110, in a view such as that along lines 3-3 (shownin FIG. 1), with dispenser distal end 641 of dispenser 640 inserted intofitting 110.

Dispenser 640 may define longitudinal dispenser axis L₁. End 641 mayinclude lateral wall 645. End 641 may include terminal surface 648.Surface 648 may define dispenser aperture 644. Aperture 644 may be adistal-most end of dispenser bore 642. Bore 642 may be parallel to axisL₁. Bore 642 may be configured to contain a fluid to be dispensed. Bore642 may be in fluid communication with aperture 644.

Dispenser 640 may be received by fitting 110. End 641 may belongitudinally inserted into fitting 110. When end 641 is inserted intofitting 110, axis L₁ may be collinear with axis L (shown in FIG. 1).Insertion of end 641 into fitting 110 may be limited by the lodging ofsurface 648 against detent 218. When surface 648 lodges against detent218, surface 648 may lodge against top 317. When surface 648 lodgesagainst detent 218, aperture 644 may be in fluid communication withopening 222.

When surface 648 lodges against detent 218, gasket 204 may be compressedbetween surface 648 and base portion 213. When gasket 204 is compressedbetween surface 648 and base portion 213, gasket 204 may be compressedbetween surface 648 and distal bottom 215 of recess. When gasket 204 iscompressed between surface 648 and base portion 213, gasket 204 may bein sealing contact with surface 648. When gasket 204 is in sealingcontact with surface 648, seal 204, wall 645, facet 210 and wall 209 maydefine region R. When gasket 204 is in sealing contact with surface 648,region R may be isolated from fluid communication with bore 642.

Dispenser 640 may include engagement surface 649. When end 641 isinserted into fitting 110, member 219 may engage surface 649. Engagementof member 219 and surface 649 may maintain gasket 204 in sealing contactwith surface 648.

FIG. 7 shows illustrative fitting 710, in a view similar to that offitting 110 shown in FIG. 4, with dispenser distal end 741 of dispenser740 inserted into fitting 710. Fitting 710 may have one or more featuresin common with fitting 110 (shown in FIG. 1).

Fitting 710 may include body 711. Body 711 may include interior wall709. Body 711 may include void 720.

Body 711 may include base portion 713. Base portion 713 may support seal704. Seal 704 may include contoured top 705. Base portion 713 maysupport detent 718. Detent 718 may include contoured face 717.

Dispenser 740 may include lateral wall 745. Dispenser 740 may includebore 742. Bore 742 may be configured to contain fluid to be dispensed.Dispenser 740 may include contoured terminal surface 748. Surface 748may be complementary to top 705. Surface 748 may be complementary toface 717.

FIG. 7 shows that dispenser 740 may be inserted into fitting 710.Insertion of dispenser 740 into fitting 710 may be limited by thelodging of surface 748 against detent 718. When surface 748 lodgesagainst detent 718, bore 742 may be in fluid communication with void720.

When surface 748 lodges against detent 718, gasket 704 may be compressedbetween surface 748 and base portion 713. When gasket 704 is compressedbetween surface 748 and base portion 713, gasket 704 may be in sealingcontact with surface 748. When gasket 704 is in sealing contact withsurface 748, seal 704, wall 745 and wall 709 may define region R1. Whengasket 704 is in sealing contact with surface 748, region R1 may beisolated from fluid communication with bore 742.

Fitting 710 may include engagement member 719. Dispenser 740 may includeengagement surface 749. When dispenser 740 is inserted into fitting 710,member 719 may engage surface 749. Engagement of member 719 and surface749 may maintain gasket 704 in sealing contact with surface 748.

Body 711 may include one or more bosses. For example, body 711 mayinclude boss 721. When dispenser 740 is inserted into fitting 710, boss721 may engage wall 745. Engagement of boss 721 and wall 745 maymaintain gasket 704 in sealing contact with surface 748.

FIG. 8 shows fitting 110 in a sectional view taken along lines 4-4(shown in FIG. 1).

FIG. 8 shows fitting 110, in a view such as that along lines 4-4 (shownin FIG. 1), with dispenser distal end 641 of dispenser 640 inserted intofitting 110.

When dispenser 640 is inserted into fitting 110, surface 648 may lodgeagainst detent 218. The lodging of surface 648 against detent 218 maycompress gasket 204. When gasket 204 is compressed, gasket 204 maysealingly contact surface 648.

When dispenser 640 is inserted into fitting 110, wall 645 may engage rim208. Engagement of rim 208 and wall 645 may align axis L₁ (shown in FIG.6) with axis L (shown in FIG. 1).

Engagement of rim 208 and wall 645 may deform rim 208. When rim 208 isdeformed by dispenser 640 and when gasket 204 is compressed by dispenser640, tensional forces may be transmitted between rim 208 and gasket 204.The tensional forces may be transmitted through member 201 and member207. The tensional forces may strengthen the sealing contact of gasket204 with surface 648 by further urging gasket 204 against surface 648.The tensional forces may strengthen the engagement of rim 208 and wall645 by wedging rim 208 further into the gap between rim 208 and wall645.

FIG. 9 is a cross-sectional view of fitting 110 with dispenser 640(shown in FIG. 6) inserted into fitting 110, taken along lines 9-9(shown in FIG. 6). Lines 9-9 may lie in a plane of abutment of surface648 (shown in FIG. 6) against detent 218 and against gasket 204. Detent218, gasket 204 and region R may lie within fitting 110.

Fluid 960 may span aperture 644. Fluid 960 may span opening 222. Fluid960 may be the fluid that bore 642 (shown in FIG. 6) may be configuredto contain.

One or more volumes of fluid may lie within an inner border of gasket204. For example, volume 962 may lie within the inner border of gasket204. Volume 962 may lie upon detent 218. Volume 962 may lie belowsurface 648 (shown in FIG. 6). Volume 962 may be contiguous with fluid960 spanning aperture 644. Fluid in volume 962 may be fluid 960. Whengasket 204 is in sealing contact with surface 648 (shown in FIG. 6), thefluid in volume 962 may be sealingly isolated from region R. When gasket204 is in sealing contact with surface 648 (shown in FIG. 6), aperture644 may be sealingly isolated from region R. When gasket 204 is insealing contact with surface 648 (shown in FIG. 6), opening 222 may besealingly isolated from region R.

FIG. 10 shows illustrative device 1000. Device 1000 may have one or morefeatures in common with fitting 110, with dispenser 640 (shown in FIG.6) inserted into fitting 110, as shown in FIG. 9. In FIG. 9, detent 218,gasket 204 and region R may lie within fitting 110; in device 1000,detent 1018, gasket 1004 and region R2 may lie within fitting 1110. InFIG. 9, syringe terminal surface 648 (shown in FIG. 6) may abut detent218 and sealingly engage gasket 204; in device 1000, a syringe terminalsurface (not shown) may abut detent 1018 and sealingly engage gasket1004. In FIG. 9, fluid 960 may span aperture 644; in device 1000, fluid960 may span an aperture of the syringe terminal surface (not shown).

Device 1000 may differ from fitting 110, with dispenser 640 (shown inFIG. 6) inserted into fitting 110, as shown in FIG. 9. In FIG. 9, anouter annular border of detent 218 may lie within an inner annularborder of gasket 204; in device 1000, an outer annular border of gasket1004 may lie within an inner annular border of detent 1018. In FIG. 9,fluid 960 may be bordered by an inner annular border of detent 218; indevice 1000, fluid 960 may be bordered by an inner annular border ofseal 1004.

One or more volumes of fluid may lie outside the outer annular border ofgasket 1004. For example, volume 1062 may lie outside the outer annularborder of gasket 1004. Volume 1062 may lie upon detent 1018. Volume 1062may lie below the terminal syringe surface (not shown) of device 1000.When gasket 1004 is in sealing contact with the terminal syringe surface(not shown) of device 1000, the fluid in volume 1062 may be sealinglyisolated from the fluid-spanned open center of device 1000. When gasket1004 is in sealing contact with the terminal syringe surface (not shown)of device 1000, the open center of device 1000 may be sealingly isolatedfrom region R2.

FIG. 11 shows illustrative device 1100. Device 1100 may have one or morefeatures in common with device 100 (shown in FIG. 1).

Device 1100 may include fitting 1110. Fitting 1110 may include body1111. Body 1111 may include body portion 1113. Body portion 1113 maysupport detent 1118.

Body portion 1113 may include recess 1112. Recess 1112 may receive seal1104. A cross-section of recess 1112 may be complementary to across-section of seal 1104. Body portion 1113 may support seal 1104.

Seal 1104 may be press-fit into recess 1112. Seal 1104 may adhere to asurface of recess 1112.

Fitting 1110 may receive dispenser 640 (shown in FIG. 6). When receivedby fitting 1110, dispenser 640 may abut detent 1118 and sealingly engageseal 1104.

FIG. 12 shows illustrative device 1200. Device 1200 may include fitting110. Fitting 110 may receive insert 102. Fitting 110 may support needle130. Fitting 110 may define longitudinal axis L (shown in FIG. 1).

Device 1200 may include needle guard 1270. Guard 1270 may engage fitting110. Fitting 110 may be longitudinally inserted into engagement withguard 1270. Fitting 110 may be twisted into engagement with guard 1270.Engagement of fitting 110 with guard 1270 may allow a dispenser, such asdispenser 640 (shown in FIG. 6), to be engaged with fitting 110 with noshifting of fitting 110 relative to guard 1270.

Fitting 110 may be stored engaged with guard 1270. Guard 1270 mayaxially surround needle 130. Guard 1270 may cover a sharp distal end ofneedle 130. Engagement of fitting 110 with guard 1270 may allow apractitioner to engage a dispenser with fitting 110 while needle 130 isaxially surrounded by guard 1270.

Guard 1270 may be removed prior to adjustment of dispenser fluid volume.

FIG. 13 shows illustrative device 1300. Device 1300 may have one or morefeatures in common with fitting 110, with dispenser 640 inserted intofitting 110, as shown in FIG. 6.

Device 1300 may include dispenser 1340. Device 1300 may include fitting1310. Fitting 1300 may be configured to receive a portion of dispenser1340.

Dispenser 1340 may include dispenser bore 1342. Bore 1342 may beconfigured to contain a fluid to be dispensed.

Dispenser 1340 may include distal end 1341. End 1341 may include lateralwall 1345.

End 1341 may support detent 1318. Detent 1318 may circumscribe dispenseraperture 1344. Aperture 1344 may be a distal-most end of bore 1342. Bore1342 may be in fluid communication with aperture 1344. Dispenser 1340may include engagement surface 1349.

End 1341 may support gasket 1304. End 1341 may include recess 1312.Recess 1312 may be configured to receive gasket 1304. Recess 1312 may beannular. Gasket 1304 may be annular. Gasket 1304 may snugly engagerecess 1312. Gasket 1304 may circumscribe detent 1318.

Detent 1318 may include dispenser aperture 1344. Aperture 1344 may be adistal-most end of bore 1342. Bore 1342 may be in fluid communicationwith aperture 1344. An inner annular border of detent 1318 may be influid communication with bore 1342.

Dispenser 1340 may include engagement surface 1349.

Fitting 1310 may include fitting body 1311. Body 1311 may support needle1330.

Body 1311 may include proximal surface 1348. Surface 1348 may defineopening 1322. Body 1311 may include void 1320. Opening 1322 may be influid communication with void 1320. Void 1320 may be in fluidcommunication with needle 1330.

Fitting 1310 may include interior wall 1309. Fitting 1310 may includeengagement member 1319.

FIG. 14 shows device 1300. FIG. 14 shows that end 1341 may be insertedinto fitting 1310. Insertion of end 1341 into fitting 1310 may belimited by the lodging of detent 1318 against surface 1348. When detent1318 lodges against surface 1348, aperture 1344 may be in fluidcommunication with opening 1322.

When detent 1318 lodges against surface 1348, gasket 1304 may bedeformed into sealing contact with surface 1348. When gasket 1304 is insealing contact with surface 1348, gasket 1304, wall 1345 and wall 1309may define region R3. When gasket 1304 is in sealing contact withsurface 1348, region R3 may be isolated from fluid communication withbore 1342.

When end 1341 is inserted into fitting 1310, member 1319 may engagesurface 1349. Engagement of member 1319 and surface 1349 may maintaingasket 1304 in sealing contact with surface 1348.

FIG. 15 shows illustrative device 1500. Device 1500 may have one or morefeatures in common with device 1300 (shown in FIG. 13).

Device 1500 may include fitting 1310. Device 1500 may include dispenser1540. Dispenser 1540 may have one or more features in common withdispenser 1340 (shown in FIG. 14). Dispenser 1540 may be inserted intofitting 1310.

Dispenser 1540 may include dispenser bore 1542. Bore 5342 may beconfigured to contain a fluid to be dispensed.

Dispenser 1540 may include distal end 1541. End 1541 may include lateralwall 1545.

End 1541 may support detent 1518. Detent 1518 may circumscribe gasket1304.

End 1541 may support gasket 1504. End 1541 may define recess 1512.Recess 1512 may be configured to receive gasket 1504. Recess 1512 may beannular. Gasket 1504 may be annular. Gasket 1504 may snugly engagerecess 1512. An inner annular border of gasket 1504 may be in fluidcommunication with bore 1542.

Dispenser 1540 may include engagement surface 1549.

Insertion of dispenser end 1541 into fitting 1310 may be limited by thelodging of detent 1518 against surface 1348. When detent 1518 lodgesagainst surface 1348, bore 1542 may be in fluid communication with void1320.

When detent 1518 lodges against surface 1348, gasket 1504 may bedeformed into sealing contact with surface 1348. When gasket 1504 is insealing contact with surface 1348, gasket 1504, wall 1545 and wall 1309may define region R4. When gasket 1504 is in sealing contact withsurface 1348, region R4 may be isolated from fluid communication withbore 1542.

When end 1541 is inserted into fitting 1310, member 1319 may engagesurface 1549. Engagement of member 1319 and surface 1549 may maintaingasket 1504 in sealing contact with surface 1348.

FIGS. 16, 17 and 18 show fitting 110 with distal end 1641 of dispenser1640 inserted into fitting 110. Dispenser 1640 may have one or morefeatures in common with dispenser 640 (shown in FIG. 6).

Dispenser 1640 may define longitudinal dispenser axis L₂. End 1641 mayinclude lateral wall 1645. End 1641 may include terminal surface 1648.Surface 1648 may define dispenser aperture 1644. Aperture 1644 may be adistal-most end of dispenser bore 1642. Bore 1642 may be parallel toaxis L₂. Bore 1642 may be configured to contain a fluid F to bedispensed. Fluid F may include a medicament. Bore 1642 may be in fluidcommunication with aperture 1644.

Dispenser 1640 may include plunger shaft 1652. Shaft 1652 may extendproximally out of a proximal-most end of bore 1642. Shaft 1652 mayinclude shaft stop 1658. Stop 1658 may be a distal face of a proximaltransverse surface of shaft 1652. Shaft 1652 may connect with shaftcollar 1654. Grooves 1656 may maintain the connection of shaft 1652 andcollar 1654. Collar 1654 may be removed from shaft 1652 by shiftingcollar 1654 out of grooves 1656.

Shaft 1652 may support plunger plug 1650. Longitudinally moving shaft1652 within bore 1642 may slide plug 1650 within bore 1642. Plug 1650may slideably seal bore 1642. When shaft 1652 is distally depressed,plug 1650 may drive fluid F distally within bore 1642.

Dispenser 1640 may be received by fitting 110. When end 1641 is insertedinto fitting 110, axis L₂ may be collinear with axis L (shown in FIG.1). Insertion of end 1641 into fitting 110 may be limited by the lodgingof surface 1648 against detent 218. When surface 1648 lodges againstdetent 218, aperture 1644 may be in fluid communication with opening222.

When surface 1648 lodges against detent 218, gasket 204 may becompressed between surface 1648 and base portion 213. When gasket 204 iscompressed between surface 1648 and base portion 213, gasket 204 may bein sealing contact with surface 1648. When gasket 204 is in sealingcontact with surface 1648, seal 204, wall 1645 and wall 209 may defineregion R5. When gasket 204 is in sealing contact with surface 648,region R5 may be isolated from fluid communication with bore 1642.

Dispenser 1640 may include engagement surface 1649. When end 1641 isinserted into fitting 110, member 219 may engage surface 1649.Engagement of member 219 and surface 1649 may maintain gasket 204 insealing contact with surface 1648.

Volume V_(prefill) of fluid F may be present in bore 1642. The volumemay be contained between aperture 1644 and distal surface 1651 of plug1650. V_(prefill) may be an initial volume of fluid F in dispenser 1640.Dispenser 1640 may be pre-filled with V_(prefill) of fluid F.Pre-filling dispenser 1640 may set distal surface 1651 of plug 1650 atlocation L_(prefill) within dispenser 1640. When surface 1651 is atL_(prefill), a distance between a proximal-most surface of dispenser1640 and a distal-most surface of collar 1654 may be distance d.

FIG. 17 shows distal surface 1651 of plug 1650 at location L_(primed).L_(primed) may be distal along axis L₂ (shown in FIG. 16) relative tolocation L_(prefill). Plug 1650 may be moved to L_(primed) by depressingshaft 1652 distally into bore 1642 as far as collar 1654 allows. Shaft1652 may be depressed distally by distance d (shown in FIG. 16). Whenshaft 1652 is depressed distally by distance d, the distal-most surfaceof collar 1654 may contact the proximal-most surface of dispenser 1640.

Depressing plug 1650 from L_(prefill) to L_(prefill) may distally drivea portion of V_(prefill) out of bore 1642. That portion may be a volumeV_(primed). Part of V_(primed) may be advanced distally into void 220.Part of V_(primed) may be advanced distally into needle 130. Part ofV_(primed) may be advanced to orifice 232. The volume of fluid remainingwithin bore 1642 may be given by the difference V_(prefill) minusV_(primed). The difference V_(prefill) minus V_(primed) may include adose volume V_(dose).

FIG. 18 shows that dose volume V_(dose) may be dispensed into target1880. V_(dose) may be dispensed into target 1880 by advancing plug 1650within bore 1642 from L_(primed) to location L_(dose). L_(dose) may bedistal to L_(primed). Plug 1650 may be advanced to L_(dose) bydepressing shaft 1652, after removal of collar 1654, distally into bore1642 as far as allowed by shaft stop 1658. When shaft 1652, afterremoval of collar 1654, is fully depressed into bore 1642, stop 1658 maycontact the proximal-most surface of dispenser 1640.

The difference L_(primed) minus L_(dose) may correspond to a maximumdelivery stroke of dispenser 1640. The difference L_(prefill) minusL_(dose) may correspond to the maximum stroke length of shaft 1652. Themaximum stroke length of shaft 1652 may be set so as to leave apredetermined volume of fluid F within bore 1642 after full depressionof shaft 1652 into bore 1642.

Processes in accordance with the principles of the invention may includeone or more features of the processes illustrated in FIG. 19. One ormore steps of the processes may be performed with all or portions of theapparatus shown in FIGS. 1-18.

Some steps of the process may be performed by a practitioner, whileother steps may be performed by others. For simplicity of presentation,the steps of the process are presented performed by a “user.”

The process may be a therapeutic process. The therapeutic process mayinclude injection of the medicament into a patient. A target volume ofthe medicament may be injected into a target tissue of a patient. Thetarget volume of the medicament may be injected into an implant. Theimplant may be implanted in the patient. The target volume may be a dosevolume called for in the therapeutic process.

FIG. 19 shows illustrative steps of process 1900 for delivering a lowvolume of fluid. Components of the apparatus may be packaged in sterilepackaging. The pre-filled syringe and the fitting may be packaged asseparate apparatus components. The fitting may be engaged with theneedle guard.

A volume of fluid pre-filling the syringe may be greater than the lowvolume to be delivered. The volume of fluid pre-filling the syringe maybe large enough to be set with more precision than may be possible werethe syringe to be pre-filled with the low volume to be delivered. Thepre-filled syringe may be capped on the distal end by a removable cap.The cap may prevent loss of fluid by leakage during storage of thesyringe. A volume of fluid containing the medicament to be delivered mayfill the syringe from the distal surface of the plunger plug to an innersurface of the cap.

The pre-filled syringe may have its shaft positioned such that thedistal surface of the plunger plug is at L_(prefill) (shown in FIG. 16).The shaft collar may be connected to the proximal end of the syringeshaft (shown in FIG. 16).

Process 1900 may begin at step 1902. At step 1902, the user may removethe fitting and the capped pre-filled syringe from the sterilepackaging.

At step 1904, the user may invert the capped syringe so that the cappedend is approximately upright.

At step 1906, the user may uncap the inverted syringe.

At step 1908, the user may fully engage the uncapped inverted syringeinto the fitting. In embodiments in which the syringe includes the seal,the fitting may support a needle and include a reservoir but may beconfigured such that it does not include a seal. In embodiments in whichthe syringe includes the reservoir, the fitting may support a needle butmay be configured such that it does not include a reservoir. Engagementof the syringe with the fitting may effect sealing contact of thesyringe and the fitting.

At step 1910, the user may remove the needle guard from the fitting.

At step 1912, the user may depress the plunger of the inverted syringe.Depression of the plunger may advance the distal face of the plug withinthe syringe bore from L_(prefill) to L_(primed) (shown in FIG. 17).Advancement of the distal face of the plug may reduce the volume offluid within the syringe by V_(primed). Advancement of the distal faceof the plug may prime the syringe engaged with the fitting.

Advancement of the plunger within the bore may be limited by the shaftcollar (shown in FIG. 16). After advancement of the shaft to L_(primed)(shown in FIG. 17), the user may remove the collar.

At step 1914, the user may insert the needle into a target area, such astarget 1880 (shown in FIG. 18).

At step 1916, the user may fully depress the plunger to the maximumdelivery stroke, injecting the dose volume of medicament into the targetarea.

Thus, apparatus and methods for low-volume medicament delivery have beenprovided. Persons skilled in the art will appreciate that the presentinvention can be practiced by other than the described embodiments,which are presented for purposes of illustration rather than oflimitation. The present invention is limited only by the claims thatfollow.

What is claimed is:
 1. A fitting for a fluid dispenser, the fittinghaving a longitudinal axis and comprising: a detent that is configuredto limit longitudinal insertion of the dispenser into the fitting bycontacting a terminal surface of the dispenser, a top of the detentdefining a first tangent plane; a seal that is configured to be deformedby the surface, into a sealing contact against the surface, the contactdefining a second tangent plane substantially coplanar with the firstplane when the surface abuts the detent, the first plane maintaining afixed orientation relative to the top throughout deformation of theseal; and a body that is configured to: receive the surface; and supportthe detent and the seal; wherein; the seal is seated in the body in arecess having a bottom; and the body includes an interiorproximal-facing facet that is disposed; more proximal than is thebottom; and more distal than is the top.
 2. The fitting of claim 1wherein the detent defines an opening configured to be placed in fluidcommunication with the dispenser.
 3. The fitting of claim 2 wherein theopening is configured to be placed in fluid communication with anaperture of the dispenser when the surface lodges against the decent. 4.The fitting of claim 1 wherein the seal circumscribes detent.
 5. Thefitting of claim 1 wherein the detent circumscribes the seal.
 6. Thefitting of claim 2 wherein: the body includes an interior wall; and thedispenser includes a lateral wall; such that, when the surface is insealing contact against the seal, and abuts the detent, the interiorwall, the lateral wall and the seal define a region that is isolatedfrom fluid communication with the dispenser.
 7. The fitting of claim 6wherein: the region is a first dead space having a first volume; thedetent, when in contact with the surface, defines a second dead spacehaving a second volume; and the second volume is no more than 1% thefirst volume.
 8. The fitting of claim 7 wherein the second dead spaceincludes one or more volumes in a region that is: transverselycoextensive with contact between the surface and the detent; andlongitudinally extensive between the surface and the detent.
 9. Thefitting of claim 7 wherein the second dead space is within the seal. 10.The fitting of claim 6 wherein the sealing contact is sufficient toprevent leakage of fluid from the dispenser to the region when thedispenser is actuated to dispense the fluid.
 11. The fitting of claim 6wherein the interior wall includes a boss that is configured to engagethe lateral wall of the dispenser.
 12. The fitting of claim 2 wherein:the dispenser is pre-filled with an initial volume of fluid; and thebody defines a void that is in fluid communication with the opening, thevoid having a void volume that is not less than 10% the initial volume.13. The fitting of claim 12 wherein the void volume is not less than 25%the initial volume.
 14. The fitting of claim 12 wherein the void volumeis not less than 50% the initial volume.
 15. The fitting of claim 12wherein the void volume is not less than 75% the initial volume.
 16. Thefitting of claim 12 wherein the void volume is not less than 90% theinitial volume.
 17. The fitting of claim 12 wherein a volume of fluiddispensed through an orifice of a needle in fluid communication with thevoid is the initial volume reduced by an amount that is not less thanthe void volume.
 18. The fitting of claim 1 wherein the seal is annular.19. The fitting of claim 1 wherein: the seal includes a proximal face;and the seal includes a distal face, spaced apart from the proximalface.
 20. The fitting of claim 19 wherein the proximal face and thedistal face are substantially parallel.
 21. The fitting of claim 19wherein: the seal includes an outer surface that extends in thelongitudinal direction; and the seal includes an inner surface thatextends in the longitudinal direction.
 22. The fitting of claim 21wherein: the distal face and the inner surface intersect at an angle ofabout 90°; and the distal face and the outer surface intersect at anangle of about 90°.
 23. The fitting of claim 1 further including a baseportion from which the detent and the seal extend longitudinally in aproximal direction, the detent including the top, the seal, in a relaxedstate, extending proximally beyond the top.
 24. The fitting of claim 23wherein the seal does not extend transversely over the top.
 25. Thefitting of claim 1 wherein the recess is configured to secure the sealsuch that a proximal end of the seal is not drawn laterally over thetop.
 26. The fitting of claim 1 wherein the axis, when the surface abutsthe detent, lies perpendicular to the surface.
 27. The fitting of claim1 wherein: the detent has a first contour; the surface has a secondcontour; and the first contour and the second contour are complementary.28. The fitting of claim 27 wherein; the seal has a third contour; andthe second contour and the third contour are complementary.
 29. Thefitting of claim 1 wherein: the seal comprises a first substance thathas a first elastic modulus; the detent comprises a second substancethat has a second elastic modulus; and the second elastic modulus isgreater than the first elastic modulus.
 30. The fitting of claim 29wherein the surface is disposed on a portion of the dispenser having athird elastic modulus.
 31. The fitting of claim 30 wherein the thirdelastic modulus is about the same as the second elastic modulus.
 32. Thefitting of claim 1 further comprising an engagement member that isconfigured to maintain the sealing contact by engaging the dispenser.33. The fitting of claim 1 wherein the fitting is configured to engage aneedle guard.